1145747-63-2

Upstream product

• 110-91-8 morpholine 
• 1145747-62-1 (3R,5S)-5-{[(benzyloxy)carbonyl]amino}-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid 
• 499-81-0 3,5-Pyridinedicarboxylic acid 
• 4591-55-3 dimethyl pyridine-3,5-dicarboxylate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 1145747-61-0 1-tert-butyl 3-methyl (3R,5S)-5-{[(benzyloxy)carbonyl]amino}piperidine-1,3-dicarboxylate 
• 191544-71-5 (3R*,5S*)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid 
• 534572-17-3 (3R,5S)-1-(tert-butoxycarbonyl)piperidine-3,5-dicarboxylic acid 
• 920297-39-8 1-(tert-butoxycarbonyl)piperidine-3,5-dicarboxylic acid 
• 914260-44-9 2,4-dioxo-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylic acid tert-butyl ester 
• 595555-70-7 1-tert-butyl 3,5-dimethyl piperidine-1,3,5-tricarboxylate 

Downstream Products

• 1145750-35-1 tert-butyl (3S,5R)-3-[({2-[(3-methoxypropyl)amino]-7,7-dimethyl-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}carbonyl)(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate 
• 1202263-39-5 tert-butyl (3S,5R)-3-[{[5-(4-methoxybutyl)-1-phenyl-1H-imidazol-4-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate 
• 1202263-37-3 tert-butyl (3S,5R)-3-[{[2-chloro-5-(4-methoxybutyl)-1-phenyl-1H-imidazol-4-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate 

Relevant academic research and scientific papers

Discovery of benzimidazole derivatives as orally active renin inhibitors: Optimization of 3,5-disubstituted piperidine to improve pharmacokinetic profile

We previously identified 2-tert-butyl-4-[(3-methoxypropyl)amino]-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]pyrimidine-5-carboxamide 3 as a potent renin inhibitor. Since 3 showed unacceptably low bioavailability (BA) in rats, structural modification, using SBDD and focused on physicochemical properties was conducted to improve its PK profile while maintaining renin inhibitory activity. Conversion of the amino group attached at the 4-position of pyrimidine to methylene group improved PK profile and decreased renin inhibitory activity. New central cores with carbon side chains were explored to improve potency. We had designed a series of 5-membered azoles and fused heterocycles that interacted with the lipophilic S3 pocket. In the course of modification, renin inhibitory activity was enhanced by the formation of an additional hydrogen bonding with the hydroxyl group of Thr77. Consequently, a series of novel benzimidazole derivatives were discovered as potent and orally bioavailable renin inhibitors. Among those, compound 13 exhibited more than five-fold of plasma renin inhibition than aliskiren in cynomolgus monkeys at dose ratio.

CRYSTAL OF AMIDE COMPOUND

Provision of crystal of 1-(4-methoxybutyl)-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]-1H-benzimidazole-2-carboxamide hydrochloride which has a superior rennin inhibitory activity and is useful as a prophylactic or therapeutic agent for hypertension and various organ disorders caused by hypertension, and the like. Crystal of 1-(4-methoxybutyl)-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]-1H-benzimidazole-2-carboxamide hydrochloride having an X-ray powder diffraction pattern showing characteristic peaks at interplanar spacings (d) of around 26.43±0.2, 7.62±0.2 and 4.32±0.2 angstroms.

AMIDE COMPOUNDS AND USE OF THE SAME

A renin inhibitor comprising a compound represented by the formula: wherein each symbol is as defined in the description, or a salt thereof or a prodrug thereof. The compound of the present invention has a superior renin inhibitory activity, and thus is useful as an agent for the prophylaxis or treatment of hypertension, various organ damages attributable to hypertension and the like

Heterocyclic compound and use thereof

Compounds represented by the formulas wherein each symbol is as defined in the specification, and a prodrug thereof have a superior renin inhibitory activity, and are useful as agents for the prophylaxis or treatment of hypertension, various organ damages attributable to hypertension and the like.